腹腔镜手术对结肠癌患者腹腔脱落癌细胞及预后的影响

目的探讨腹腔镜手术对结肠癌患者腹腔脱落癌细胞和术后复发转移的影响。方法经病理诊断为结肠癌患者159例,按患者自愿的方法分成腹腔镜手术组（腹腔镜组）和开腹手术组（开腹组）。采用细胞学方法检测肿瘤切除前后腹腔脱落癌细胞,比较两组病例在肿瘤切除前后腹腔脱落肿瘤细胞阳性率、术后复发转移率和3年生存率。结果腹腔镜组与开腹组患者肿瘤切除前腹腔脱落肿瘤细胞阳性率分别为12．2％（9／74）和15．3％（13／85）,两组比较,差异无统计学意义（P=0．718）;肿瘤切除后则分别为20．3％（15／74）和30．6％（26／85）,两组比较,差异也无统计学意义（P=0．138）。术后随访4～45月,术后3年腹腔镜组与开腹组患者局部复发率分别为13．6％（8／59）和8-8％（6／68）（P=0．455）,远处转移率分别为11．9％（7／59）和17．6％（12／68）（P=0．416）,两组比较差异无统计学意义;3年生存率则分别为79．7％和80．0％（P=0．998）,差异亦无统计学意义。结论腹腔镜手术并未增加结肠癌患者术后复发转移的概率,术后3年生存率与开腹手术相当。     

腹腔镜结直肠癌切除术在老年病人中的应用

目的探讨老年病人施行腹腔镜结直肠癌切除术的可行性和安全性。方法2003年3月。2006年8月，我院共为142例70岁以上的老年病人施行结直肠癌根治切除术，其中腹腔镜手术75例，开腹手术67例，对两组临床疗效和并发症进行回顾性对比分析。结果腹腔镜组中转开腹手术4例，中转开腹率5．3％。腹腔镜组手术时间长于开腹组[（221．5±36．2）min vs（188．1±55．1）min，t=4．311，P=0．000]。两组均无切缘阳性病例，切除淋巴结数差异无显著性。腹腔镜组术后总的并发症发生率为5．3％（4／75），无围手术期死亡；而开腹组为25．4％（17／67），明显高于腹腔镜组（x^2=11．277，P=0．001），其中7例为较严重的心肺并发症，因肺炎死亡1例。两组术后住院时间和总费用差异无统计学意义（P〉0．05）。结论腹腔镜结直肠癌切除术应用于老年病人安全可行，可以降低并发症发生率。     

腹腔镜直肠全系膜切除术治疗中、低位直肠癌的临床安全性对比研究

目的：探讨腹腔镜直肠全系膜切除治疗中、低位直肠癌手术的安全性。方法：回顾性对比分析我院2002年12月～2005年12月开腹直肠癌全系膜切除的病例（开腹组52例），以及2003年1月～2006年6月腹腔镜直肠癌全系膜切除的病例（腹腔镜组49例）。结果：腹腔镜组与开腹组一般资料差异无显著性。与开腹组比较，腹腔镜组术中出血量少[直肠癌前切除术（160±106）ml（n=37）vs（298±186）ml（n=36），t=-3．908，P=0．000；腹会阴联合直肠癌根治术（180±153）ml（n=10）vs（356±170）ml（n=14），t=-2．604，P=0．016]。腹腔镜组肠道功能恢复时间早于开腹手术组[（2．4±1．8）dVS（3．6±1．5）d，t=-3．648，P=0．000]。腹腔镜组总并发症的发生率低于开腹组[14．3％（7／49）g844．2％（23／52），x^2=10．834，P=0．001]。两组清扫淋巴结的数目无差异（12．7±6．5VS13．6±7．0，t=-0．668，P=0．505），下切缘均为阴性。腹腔镜组45例（91．8％）随访2～42个月，开腹组47例（90．4％）随访6～42个月，局部复发率分别4．4％（2／45）、4．3％（2／47）。结论：腹腔镜直肠全系膜切除治疗中、低位直肠癌安全、可行。     

肠内营养用于术前肠道准备对结直肠癌患者腹腔和肠腔脱落癌细胞及复发转移的影响

目的探讨术前肠内营养代替肠道准备对结直肠癌患者腹腔和肠腔脱落癌细胞及转移复发的影响。方法2007年3月至2011年12月问前瞻性人组120例结直肠癌者,按随机数字表法随机分为试验组和对照组,每组60例。试验组于术前3d起每日口服30ml／kg肠内营养液,不进行灌肠,不口服泻药和抗生素;对照组采用传统肠道准备,包括术前禁食、口服抗生素和清洁灌肠。两组患者均于开腹后用400ml生理盐水冲洗肿瘤所在局部腹腔,抽取腹腔冲洗液200ml,迅速送检;并于肿瘤切除后肠吻合前,用1000ml生理盐水灌洗远端结直肠腔,收集肠腔冲洗液500ml,迅速送检。比较两组患者腹腔和肠腔内脱落的癌细胞阳性率及术后并发症发生率和复发转移率。结果试验组患者腹腔和肠腔内脱落癌细胞阳性率分别为8．3％（5／60）和15．0％（9／60）．明显低于对照组患者的12．5％（13／60）和31．7％（19／60）（P=0．041和P=O．031）。试验组和对照组分别有55例和57例患者完成随访,随访时间16—46个月;两组局部复发率[5．5％（3／55）比7．0％（4／57）,P=O．733]、远处转移率[10．9％（6／55）比10．5％（6／57）,P=O．984]和3年总体生存率（80％比78％,P=O．312）的差异均无统计学意义。结论术前肠内营养可减少结直肠癌患者腹腔和肠腔脱落癌细胞的阳性率,但并不影响术后局部复发率和远处转移率。     

腹腔镜胃癌根治术后腹腔冲洗液CEA mRNA的变化和意义

目的探讨腹腔镜胃癌根治术对腹腔脱落癌细胞的影响。方法收集44例行腹腔镜胃癌根治术患者胃癌切除前后腹腔冲洗液，并以RT—PCR方法检测腹腔冲洗液CEAmRNA表达情况。结果腹腔镜胃癌根治术患者CEAmRNA表达胃癌未切除时阳性率为27．3％（12／44），切除后阳性率为36．4％（16／44），两组之间差异无统计学意义（P〉0．05）。结论腹腔镜胃癌根治术不增加腹腔胃癌细胞的脱落。     

结直肠良、恶性息肉微创治疗的临床研究

目的探讨结肠镜、腹腔镜及双镜联合治疗结直肠息肉的适应证和疗效。方法2004年1月～2006年12月，全结肠镜愉奄发现直径〉1cm的结直肠息肉共378例。结肠镜圈套器摘除319例，结肠镜黏膜切除术（endoscopic mucosal resection，EMR）11例，腹腔镜辅助结肠镜下治疗7例，结肠镜辅助腹腔镜楔形切除术6例，结肠镜辅助腹腔镜肠段切除术3例，腹腔镜结直肠癌根治术32例。结果腹腔镜辅助结肠镜治疗组与结肠镜辅助腹腔镜局部切除术组均未出现一例并发症，结肠镜圈套器摘除组中1．6％（5／319）出现并发症。结肠镜组肿瘤残留11例，追加腹腔镜结直肠癌根治术8例。随访中，EMR术1例肿瘤残留，追加腹腔镜结直肠癌根治术。结肠镜辅助腹腔镜楔形切除术中2例为浸润性结直肠癌，追加腹腔镜结直肠癌根治术。结论大部分结直肠良性息肉可以通过单纯结肠镜的方法得到治疗；双镜联合的治疗方式对于结肠镜治疗困难的结直肠息肉是安全、可行的治疗方法。     

腹腔镜结直肠癌根治术对肿瘤细胞微转移影响的研究

目的 探讨腹腔镜结直肠癌根治术对术后肿瘤微转移的影响。方法 以细胞角蛋白20（cytokeratin，CK-20）mRNA为靶基因，运用逆转录一聚合酶链反应方法（RT-PCR），检测48例结直肠癌患者手术前后外周血肿瘤细胞数鞋的变化。结果 腹腔镜手术组术后外周血肿瘤细胞增加数量高于传统开腹手术组（P〈0．05）。腹腔镜手术组术后外周血肿瘤细胞数量增加的程度与患者年龄无关（P〉0．05）而与增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）阳性率有明显的关系（P〈0．05）。结论 腹腔镜结直肠癌根治术有增加术后肿瘤血行转移的危险性；PCNA≥50％的患者如果行腹腔镜结直肠癌根治术，术后发生血行转移的危险性更大。     

中晚期结直肠癌191例腹腔镜与开腹根治术的疗效比较

目的比较分析应用腹腔镜下进展期结直肠癌根治术的可行性、肿瘤根治性及临床疗效。方法分析广东省人民医院2006年6月至2007年12月收治的191例进展期结直肠癌患者的临床资料。结果根据随机数字表进行分组,98例接受腹腔镜手术,93例接受传统开腹手术。腹腔镜手术组中5例（5．1％）中转开腹手术。腹腔镜手术组术中出血量为（87．2±27．1）ml,明显少于传统开腹手术组的（279．5±189．4）ml（P=0．011）。腹腔镜手术组48h内肛门排气和离床活动的患者分别占37．8％（37／98）和30．6％（30／98）,明显高于传统开腹手术组的6．5％（6／93,P=0．000）和3．2％（3／93,P=0．000）。传统开腹手术组术后需要使用麻醉性止痛药止痛的患者占133％（13／98）．明显高于腹腔镜手术组的61．3％（57／93）（P=-0．000）。腹腔镜手术组平均总住院时间为（8．9±5．9）d．明显低于传统开腹手术组（12．1±7．6）d（P=0．036）。两组其他临床因素（性别、年龄、肿瘤部位和TNM分期、手术切除方式、收获淋巴结数目、术后并发症发生率等）比较,差异无统计学意义（P〉0．05）。结论进展期结直肠癌行腹腔镜根治术安全可行．能达到与开腹同样的效果。     

多基因联合提高结直肠癌甲基化检测阳性率的研究

目的探讨联合检测Vimentin、sFRP1和HPP1基因甲基化对提高结直肠癌甲基化阳性率的意义。方法收集90例结直肠癌（结直肠癌组）和60例腺瘤性息肉（腺瘤组）患者及20例结直肠正常组织（正常对照组）标本,提取组织标本的DNA,采用甲基化特异性PCR（MSP）检测Vimentin、sFRP1和HPP1基因甲基化状态。分析其与结直肠癌的关系及甲基化阳性率。结果结直肠癌组Vimentin、sFRP1和HPP1基因甲基化率分别为66．7％（60／90）、68．9％（62／90）和72．2％（65／90）;腺瘤组则分别为53.3％（32／60）、55．0％（33／60）和50．0％（30／60）;正常对照组分别为0、0和5．0％（1／20）。结直肠癌组3个基因甲基化阳性率均高于腺瘤组和正常对照组（P〈O．05）。3个基因甲基化联合检测诊断结直肠癌和腺瘤的阳性率分别为93．3％（84／90）和76．7％（46／60）,高于单个基因检测的甲基化阳性率（P〈0．05）。3个基因甲基化状态与本组结直肠癌患者的性别、年龄、肿瘤部位、淋巴结转移、远处转移及TNM分期无关（P〉0．05）。结论Vimentin、sFRP1和HPP1基因启动子甲基化水平在结直肠癌组织中升高．其联合检测明显提高了结直肠癌甲基化检测阳性率．有可能成为结直肠癌早期诊断的甲基化检测方案。     

腹腔镜与开腹结直肠癌根治术对腹膜结构损伤的前瞻性对照研究

目的探讨腹腔镜与开腹结直肠癌根治术对腹膜结构损伤的差异。方法将符合纳入标准的50例结直肠癌患者分为腹腔镜组（LO组,27例）和开腹组（CO组,23例）,前瞻胜比较两组手术时间、术中失血量、淋巴结清除数及其阳性数目、肠管切除长度、肿瘤距两端切缘距离和切缘病理学：采用光镜和扫描电镜观察两种手术方式对腹膜结构损伤的程度。结果L0组手术时间比CO组短[（150．6±39．5）min比（183．0±39．2）min,P〈0．05],失血量显著少于CO组[（80．0±75．2）ml比（234．5±235．3）ml,P〈0．01]。两组切除标本长度、肿瘤距两端切缘距离、清除淋巴结总数及淋巴结阳性数目差异均无统计学意义（P〉0．05）。两组标本切缘均为阴性。光镜观察：CO组肠管浆膜完整性受损程度、系膜脂肪细胞与间皮细胞覆盖脱失程度、红细胞及炎性细胞聚集程度均较LO组严重（P〈0．01）;扫描电镜观察：CO组结直肠浆膜覆盖完整性受损程度、间皮改变程度和基底膜暴露程度均较LO组严重。结论在达到同等根治切除清扫程度下．腹腔镜结直肠癌根治术比传统开腹手术对腹膜结构损伤轻。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.